The domestic cat is a model for 36 human physiological disorders ranging from oncologic dysfunctions to AIDS. Understanding the reproduction of the cat ensures the propagation of feline models for studying these conditions. This is one of the few projects worldwide focusing on characterizing and understanding the reproductive biology of the domestic cat and its wild relatives. Although a wide array of events are studied, the project concentrates on developing a basic understanding of fertilization and embryogenesis. Findings are relevant to (1) studies of cellular and intracellular fertilization mechanisms, (2) the significance of teratospermia (the ejaculation of many malformed sperm, a condition common to felids and humans), (3) propagation of genetically valuable laboratory animals and endangered species, and (4) genetic mapping studies and plans to deliver molecularly cloned genes into early-stage pre-implantation embryos. Particularly exciting is the translation of basic information into practical tools (especially artificial insemination [AI] and in vitro fertilization [IVF]/embryo transfer) that have usefulness for producing genetically valuable laboratory cats and endangered species. Studies have focused on identifying subcellular mechanisms to explain why even normally-shaped sperm from teratospermic males are compromised in fertilization ability. All sperm from teratospermic males may be deficient in phosphorylation mechanisms, suggesting a deficiency in the physiological cascade leading to the acrosome reaction. We also generated the first characterization of natural embryogenesis in the domestic cat and compared in vitro development of these embryos to those produced by IVF. These data will be crucial in future studies for maximizing survival of genetically altered embryos. Studies apply "assisted" reproduction to propagating endangered felids. Living offspring have been produced using fresh spermatozoa and AI in the cheetah, puma, clouded leopard and tiger. A living offspring has been produced in the leopard cat (a species useful in hybridization studies to develop a high resolution genetic linkage map of the cat) using AI and frozen-thawed sperm.